tbuckley/cabot-search huggingface dataset:
In This Issue
Journal: Journal of Clinical Investigation (2006)

A tough Itch to scratchAlthough extensive studies have been performed to understand the induction of T cell tolerance, the link between Th2 tolerance and control of allergic inflammation is not well understood.Here, Venuprasad and colleagues provide evidence that MEKK1/JNK signaling converges with the Itch-mediated protein ubiquitination pathway in the control of Th2 tolerance and allergic asthma (pages 1117-1126).The authors used a MEKK1 mutant and JNK1 -/-mice to demonstrate that, like Itch -/-T cells, T cells from MEKK1 mutant or JNK -/-mice are also resistant to the induction of tolerance.The authors then linked Th2 tolerance to asthma by combining an in vivo tolerance protocol using high-dose soluble antigen with a mouse model of asthma.Although asthma could be prevented with high-dose soluble antigen pretreatment in control mice, mice lacking the Itch E3 ligase still developed an allergic reaction.Thus, these results highlight a novel genetic pathway linking MEKK1/JNK signaling to E3 ligase-mediated protein ubiquitination, which is critical in the induction of Th2 tolerance and airway inflammation.
Thirty-Second Annual Conference of The National Council on the Aging, Inc.
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Thirty-Second Annual Conference of The National Council on the Aging, Inc. Get access JNCI: Journal of the National Cancer Institute, Volume 68, Issue 1, January 1982, Page 175, https://doi.org/10.1093/jnci/68.1.175-a Published: 01 January 1982
Abstract 4559: Tumor-derived Galectin-1 promotes tumor growth in an orthotopic C57Bl/6 NB mouse model
Authors: Stefan Fest
Journal: Cancer Research (2019)

Abstract Question We recently introduced the carbohydrate-binding protein Galectin-1 (Gal-1) as a novel tolerogeneic molecule in neuroblastoma (NB). NB-secreted Gal-1 suppressed the maturation of dendritic cells (DC) and inhibited T cell function. Here, we focused on the question whether tumor-derived Gal-1 is the decisive factor to promote tumor growth in our model for NB. Methods C57Bl/6J-derived orthotopic growing NB cells (named NB975A) were used for all culture as well in vivo experiments. Gal-1 knock-down clones (GL) were generated by stable transfection of wt NB975A cells (NBA) with the antisense Gal-1 expression vector (NBA-GL), (kindly provided by Dr. Rabinovich). Blasticidine resistant (5 mikrogram/ml) transfectants were cloned by limited dilution. Protein expression of Gal-1 was determined by Western blot. Orthotopic NB tumors were generated in C57Bl/6J wild type and Gal-1-knock-out (Lgals-/-) female mice by subcapsular tumor cell injection of NBA-GL or wild type NBA (1x106, 0,1 ml PBS) into the left kidney. Primary tumor growth was analyzed by using high frequency ultrasound measurement. Mice were sacrificed 23 days after tumor inoculation and tumor tissue was harvested for further analysis. Results NBA-GL showed 50% reduced protein expression of Gal-1 compared to control wild type NBA cells. In vitro viability and proliferation of the tumor cells was not affected by the transfection. Mice inoculated with NBA-GL cells had significantly smaller primary tumors when compared with control animals that received the NBA cells. Gal-1 sufficient tumor cells injected in Gal-1-deficient host mice grew normally. Conclusion Tumor-derived Gal-1 and not its expression in host is critical for the promotion of tumor growth. Citation Format: Stefan Fest. Tumor-derived Galectin-1 promotes tumor growth in an orthotopic C57Bl/6 NB mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4559.
The paper chase
Authors: B. Dan
Journal: JAMA (1983)

The trail begins innocently enough—just a typeset line in the 1978 Author Index of the<i>Cumulated Index Medicus:</i><b>Darsee JR:</b>EKG changes and anaphylaxis [letter] South Med J 70(10):1249, Oct 77. For the next month the index shows another letter by the same author in a different journal; two months later there is an another, and a few months later another. Rapidly the citations in the<i>Index Medicus</i>change. Letters to the editor are replaced by short, single-authored papers. Soon, longer manuscripts appear in the line listings, with two, then three, then four and five authors. With time, the names of the journals become more prestigious, small papers give way to substantial works, and researchers of national and international stature are listed as coauthors with increasing frequency. For the past five years, Darsee's name appears on an astounding 116 articles listed in the<i>Science Citation Index</i>(which does not include
Masthead
Authors: Jurg Reichen, Paul Berk, New Yorh, Andres Blei, Herbert Bonkovsky, M Worcester, Allan Wolkoff, Raymond Koff, Adrian Bisceglie, St Louis, Michael Gerber, Robert Glickman, Ann Hubbard, Albert Jones, San Francisco, Willis Maddrey, Esteban Dallas, Kunio Mezey, T Liang, M Boston, Irwin Arias, Steven Schenker, San Antonio, Michelle Britton, Debra Segura, Data Meyer, D Montgomery Bissell, Sun Francisco, Anthony Tavill, Eugene Schiff, John Gollan, Joseph Councillors, Neil Bloomer, Los Kaplowitz, C Angeles, Nicholas Larusso, Marion Peters, Jay Hoofnagle, Esteban Mezey, Michael Baltimore, William Lee, Jules Dienstag, Joseph Bloomer, Andrew Klein, Glen Arm, Anna Lok, Kevin Mullen, Robert Cleveland, C S A N Francisco, Adrian Reuben, W Hepatology
Journal: Hepatology (1995)
Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway
Authors: Michael R. Blackburn, Chun G. Lee, Hays W.J. Young, Zhou Zhu, Janci L. Chunn, Min Jong Kang, Suman K. Banerjee, Jack A. Elias
Journal: Journal of Clinical Investigation (2003)

IL-13 is an important mediator of inflammation and remodeling. We hypothesized that adenosine accumulation, alterations in adenosine receptors, and adenosine–IL-13 autoinduction are critical events in IL-13–induced pathologies. To test this, we characterized the effects of IL-13 overexpression on the levels of adenosine, adenosine deaminase (ADA) activity, and adenosine receptors in the murine lung. We also determined whether adenosine induced IL-13 in lungs from ADA-null mice. IL-13 induced an inflammatory and remodeling response that caused respiratory failure and death. During this response, IL-13 caused a progressive increase in adenosine accumulation, inhibited ADA activity and mRNA accumulation, and augmented the expression of the A1, A2B, and A3 but not the A2A adenosine receptors. ADA enzyme therapy diminished the IL-13–induced increase in adenosine, inhibited IL-13–induced inflammation, chemokine elaboration, fibrosis, and alveolar destruction, and prolonged the survival of IL-13–transgenic animals. In addition, IL-13 was strongly induced by adenosine in ADA-null mice. These findings demonstrate that adenosine and adenosine signaling contribute to and influence the severity of IL-13–induced tissue responses. They also demonstrate that IL-13 and adenosine stimulate one another in an amplification pathway that may contribute to the nature, severity, progression, and/or chronicity of IL-13 and/or Th2-mediated disorders.
Primary osteoarthrosis of the knee or hip. Prevalence of Heberden nodes in relation to age and sex
Authors: H. Yazici
Journal: JAMA (1975)

One hundred twenty probands with primary osteoarthrosis of the hip or knee were examined prospectively; there were 194 controls. In addition, 193 patients with hip or knee arthrosis were examined retrospectively. Restriction of rotation on physical examination accurately differentiated arthrotic hips from normal ones. Among women, 38% of the controls and 49% of the probands had Heberden nodes (<i>P</i>&gt;.1). Their prevalence increased with age. Individuals with multiple arthrosis joints were not older than those with single joint involvement, and they had a similar prevalence of nodes. Of the probands, 14% had arthrosis of both the knee and hip. Of those with bilateral hip arthrosis, 33% had knee arthrosis as well. Heberden nodes are unrelated to osteoarthrosis of the knee or hip. Knee and hip arthroses frequently occur together and remain confined to the initially affected joints. They may have a common cause. (<i>JAMA</i>231:1256-1260, 1975)
COPD exacerbations
Authors: M CAMPBELL HAGGERTY
Journal: Thorax (2001)

COPD exacerbationsWe read with interest the paper by Cotton and associates 1 on early discharge for patients with exacerbations of chronic obstructive pulmonary disease and the accompanying editorial by Killen and Ellis. 2 In both publications the 1991 study of our RespiCare home care programme was referenced, 3 and both asserted that our programme was not cost eVective.In fact, our study reached the opposite conclusion-namely, that the Respi-Care programme was shown to be cost eVective.Actual direct care charges in US dollars were used in our calculations of both pre-programme and on-programme costs.Additionally, administrative costs of operating RespiCare were added into the onprogramme costs.Our findings showed that, while hospitalisation costs substantially decreased during the programme, home care costs increased.However, the decrease in hospital costs more than oVset the subsequent increase in home care costs, with a total cost savings of $328 US dollars per patient per month or $3956 per year being realised for those on the RespiCare programme.Although the emphasis of the work was on improvements in clinical outcome, the cost savings were a significant and important aspect of our study.I hope this clarifies any misunderstanding created by the recent articles.
A family outbreak of serious streptococcal infection
Authors: P. Cannaday
Journal: JAMA (1976)

A localized outbreak of scarlet fever was caused by an M-nontypable T-1 (NT/1) group A β-hemolytic<i>Streptococcus</i>. The result was a fatal outcome in a 5-year-old child and a near fatality in his 10-year-old sibling. The outbreak was confined to family units that had members with whom the children were close playmates. Extensive epidemiologic studies in neighborhood schools and local hospital emergency rooms did not demonstrate a dissemination of the causative serotype in the community. (<i>JAMA</i>236:585-587, 1976)
Abstract 5566: Recovery of Erk Signaling Restores Defective Angiogenesis and Arteriogenesis in Synectin-Deficient Animals
Authors: Bin Ren, Arpita Mukhopadhyay*, Anthony A Lanahan, Zhen W Zhuang, Karen L Moodie, Randall T Peterson, Michael Simons
Journal: Circulation (2008)

Background : Arterial morphogenesis is an important and poorly understood process. We have previously demonstrated that disruption of synectin gene expression in mice and zebrafish results in impaired arterial development and branching morphogenesis. Synectin null endothelial cells demonstrate reduced VEGF responsiveness in terms of migration, proliferation and differentiation and ERK-1/2 activation (Chittenden et al, Dev Cell 2006). Since ERK has been established as major participants in the regulation of cell growth and differentiation and Erk activation has been previously linked to arterial morphogenesis, we evaluated whether activation of Erk signaling in synectin disrupted mice and zebrafish as well as synectin KO arterial endothelial cells (ECs) would restore defective migration, arterial differentiation, angiogenesis and arteriogenesis. To stimulate ERK signaling we used partial inhibition of PI3-K activity to reduce Akt-dependent suppression of Raf1 activation or introduction of constitutively active ERK construct. Methods : In vitro studies were conducted with primary arterial ECs isolated from synectin wild type (WT) and knock out (KO) mice. In vivo studies were carried out in WT and synectin deficient mice and synectin knockdown zebrafish embryos. Results: Exposure of synectin −/− arterial EC to two selective PI3K inhibitors GS4898 or LY294002 in vitro restored ERK activation in a dose-dependent manner and returned cell migration and in vitro branching morphogenesis to wild type levels. Transduction of a constitutively active ERK construct in vitro or in a Matrigel model in vivo had similar effect. Systemic treatment of synectin −/− mice with GS4898 fully restored impaired angiogenesis and arterial morphogenesis in adult animals in the setting of hindlimb ischemia. Similar treatment nearly completely restored arterial development defects in zebrafish treated with a synectin morpholino. Conclusions: ERK activation plays a key role in arteriogenesis both in adult tissues and during embryonic development. Activation of compromised ERK-1/2 signaling may be a novel therapeutic intervention to stimulate arteriogenesis.
Peripheral-blood mononuclear cell responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C
Authors: H Schupper
Journal: Hepatology (1993)

Peripheral blood mononuclear cell proliferative responses in vitro to recombinant yeast or Escherichia coli hepatitis C virus fusion proteins were evaluated in 20 patients with chronic hepatitis C who were reactive for antibody to hepatitis C virus (on enzyme immunoassay, version 2.0, and a four-antigen recombinant immunoblot assay). Twenty age-matched, healthy individuals negative for antibody to hepatitis C virus were used as a control group. Peripheral-blood mononuclear cells from all chronic hepatitis C patients with antibodies to hepatitis C virus antigens c22 and c100-3 proliferated in vitro in response to the corresponding recombinant hepatitis C virus fusion protein. Peripheral-blood mononuclear cells from 75% of patients infected with hepatitis C virus proliferated in response to cytidine monophosphate-keto-3-deoxyoctulosonic acid–core recombinant antigen but there was no proliferative response to cytidine monophosphate-keto-3-deoxyoctulosonic acid–EF (derived from the NS5 region). All hepatitis C virus–infected patients had 33c antibody, but peripheral-blood mononuclear cells from only 9 of 14 (64%) proliferated in vitro in response to 33c. Ninety-five percent of all hepatitis C virus–in-fected patients had peripheral-blood mononuclear cells that proliferated in response to at least one recombinant hepatitis C virus fusion protein. The numbers and percentages of CD3 T cells, CD19 B cells and natural killer cells from patients with chronic hepatitis C virus infection did not differ from those in the healthy control group. However, the number of non-major histocompatibility complex–restricted cytotoxic T cells (CD3-positive, CD56-positive, CD16-positive) was increased in patients with chronic hepatitis C virus infection (p < 0.05). (HEPATOLOGY 1993;18:1055-1060).
The Essentiality of Folate for the Maintenance of Deoxynucleotide Precursor Pools, DNA Synthesis, and Cell Cycle Progression in PHA-Stimulated Lymphocytes
Authors: S. Jill James, Barbara J. Miller, David R. Cross, Lynda J. McGarrity, Suzanne M. Morris
Journal: Environmental Health Perspectives (1993)

The fidelity and progression of DNA synthesis is critically dependent on the correct balance and availability of the deoxynucleoside triphosphate (dNTP) precursors for the polymerases involved in DNA replication and repair.Because folate-derived one-carbon groups are essential for the de novo synthesis of both purines and pyrimidines, the purpose of this study was to determine the effect of folate deprivation on deoxynucleotide pool levels and cell cycle progres- sion.Primary cultures of phytohemagglutin (PHA)-stimulated splenocytes were used as the cel- lular model.T-cells and macrophages were purified from spleen cell suspensions obtained from F344 rats and recombined in culture.The cells were harvested after a 66-hr incubation with PHA and analyzed for nucleotide levels by reverse-phase HPLC with diode array detection.The proportion of cells in the different phases of the cell cycle was determined by bivariate flow cytometric measurement of bromodeoxyuridine (BrdU) incorporation and DNA content (pro- pidium iodide staining).PHA-stimulated T-cells cultured in medium lacking folate and methio- nine manifested significant decreases in the deoxynucleotides dCTP, dTMP, dGTP, and dATP relative to cells cultured in complete medium.The reduction in dNTP pools was associated with a decrease in the corresponding ribonucleotide pools.Flow cytometric analysis revealed a 2- fold increase in S and G2/mitosis (GJM) DNA content in PHA-stimulated cells cultured in the medium lacking folate and methionine, which suggests a delay in cell cycle progression.These alterations in DNA content were accompanied by a 5-fold decrease in BrdU incorporation rela- tive to PHA-stimulated cells cultured in complete medium.Supplementation of the deficient medium with folate resulted in normalization of dNTP content and BrdU incorporation.The data are consistent with the interpretation that folate deprivation results in reduced dNTP lev- els that may retard DNA synthesis and cell cycle progression.
What's new in the other general journals
Authors: Alison Tonks
Journal: BMJ (2006)

People with psoriasis seem to have an increased risk of heart attack. The link is particularly noticeable in younger people with severe disease; in a large cohort study of patients from UK general practices, 30 year old patients with severe disease were more than three times more likely to have a heart attack than matched controls (relative risk 3.10 (95% CI 1.98 to 4.86)). The relative risk for 30 year olds with mild disease was a lower but still significant 1.29 (1.14 to 1.46). Credit: JAMA Psoriasis is the commonest autoimmune disease mediated by type 1 T helper (Th1) cells and the authors think it likely that immunological mechanisms are responsible. A similar association been reported among patients with rheumatoid arthritis, another disease mediated by Th1 cells. Credit: JAMA It's impossible to be certain, however. Although these authors controlled for the traditional risk factors for heart disease such as hypertension, smoking, and dyslipidaemia, they weren't able to rule out the possibility that the treatment, not the disease, increased patients' risk of a heart attack. Data on anti-inflammatory drugs for psoriatic arthritis would have been useful, for example. Whatever the reason, psoriasis seems to be a risk factor for heart attack. Doctors should encourage young people with the disease to protect their coronary arteries from other insults such as smoking. JAMA 2006;296; 1735–41 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Traditional clinical trials don't really do justice to treatments for Alzheimer's disease because they rarely mimic the complex world of clinical practice where patients and their symptoms vary over time, and drug doses are titrated up and down or stopped altogether because of side effects. To overcome some of these problems, US researchers designed a more pragmatic trial to test whether widely used atypical antipsychotic drugs were useful in the real world for controlling patients' behavioural problems. They weren't. About half … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DGelfand%26rft.auinit1%253DJ.%2BM.%26rft.volume%253D296%26rft.issue%253D14%26rft.spage%253D1735%26rft.epage%253D1741%26rft.atitle%253DRisk%2Bof%2Bmyocardial%2Binfarction%2Bin%2Bpatients%2Bwith%2Bpsoriasis.%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.296.14.1735%26rft_id%253Dinfo%253Apmid%252F17032986%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.296.14.1735&link_type=DOI [3]: /lookup/external-ref?access_num=17032986&link_type=MED&atom=%2Fbmj%2F333%2F7573%2F835.atom [4]: /lookup/external-ref?access_num=000241103400021&link_type=ISI
Infectious Diseases
Authors: Mark Y. Stoeckle
Journal: JAMA (1996)

Mortality due to infectious diseases appears to be increasing.<sup>1</sup>Factors that are thought to be important include microbial evolution, population growth, particularly in urban megacities in the less developed world, climate change, environmental habitat disruption, and large-scale movements of persons across international borders.<sup>2</sup>Recognition of the continued importance of microbial threats to health and of the need to understand the complex factors that underlie the emergence and reemergence of infectious diseases has led to the establishment of new national and global surveillance systems.<sup>3</sup> The dynamic and unpredictable nature of infectious diseases was highlighted by an unanticipated outbreak of Ebola virus hemorrhagic fever in Kikwit, Zaire.<sup>4</sup>From January to June 1995, 315 persons developed the disease and 244 died, a case fatality rate of 77%. Only 4 previous outbreaks of Ebola virus infection in humans have been recognized, and the most recent was 15 years ago in
Electromyography
Authors: Bruce A. Ames
Journal: JAMA (1974)

<h3>To the Editor.—</h3> May I comment on the letter of Dr. George H. Kraft (227:1009, 1974)? In spite of the fact that it would be difficult to find fault with Dr. Kraft's logic as regards the purely technical and theoretic aspects of electromyography and the value of its contribution to clinical medicine in the proper hands, I would like to bring to his attention the fact that the neurological sciences have apparently not evolved to the point where it is easy to obtain reasonable electromyographic evaluations. As a clinician in practice, I find that neurologists are rarely interested in or able to perform electromyograms well. In a large number of cases, one must rely on other clinical data without what would be reassuring and valuable information, were the procedure to be performed at the hands of a true professional. I would, however, suggest that a technically capable individual who was
Textbook of Medical Physiology
Authors: Panayotis G. Iatridis
Journal: JAMA (1991)

The eighth edition of the<i>Textbook of Medical Physiology</i>by Arthur C. Guyton, MD, is similar to the seventh edition with few changes or rearrangements. It is shorter by 67 pages (6.6%). The former Unit II discussion of blood cells, immunity, and blood clotting has been moved to Unit VI, where it follows the description of cardiovascular, renal, and acid-base physiology. Chapters 11 and 12, which deal with normal and abnormal electrocardiograms, have been significantly improved. Unit IV, which describes the circulation of blood, has been rearranged and updated. The nervous system material has been rearranged and ends with chapter 61 describing cerebral flow, cerebrospinal fluid, and brain metabolism. Dr Guyton continues to present physiological principles in molecular and physical terms and introduces a new feature—two print sizes. Large print describes fundamental physiological information that medical students need to know. Smaller print represents nonbasic physiological information such as anatomy, chemistry,